Field of the Invention
The invention relates to methods and devices for combined measurements of ion mobility and mass spectra or combined separation of ions according to ion mobility and mass to charge ratio respectively.
Description of the Related Art
Several ion species, such as monomers and dimers, but also ions of several molecular configurations (isomers) of the same substance, are usually formed in an ion source from molecules present in a sample. Every ion species has a characteristic mobility. Isomeric ions with the same charge-related mass m/z but different collision cross-sections have different mobility in a gas of the same temperature, pressure and composition. Isomers of the smallest geometric collision cross-section possess the greatest mobility and therefore the highest drift velocity Vd through the gas. Unfolded protein ions undergo more collisions than tightly folded proteins. Protein ions which are unfolded or partially folded therefore encounter more collisions and arrive at the end of the drift region later than strongly folded ions of the same mass. But structural isomers, for example proteins with glycosyl, lipid or phosphoryl groups at different sites, also have different collision cross-sections, which allows them to be distinguished by measuring their mobility.
U.S. Pat. No. 5,905,258 (Clemmer et al.) discloses a hybrid ion mobility and time-of-flight mass spectrometer comprising an ion source coupled to a mobility separator which feeds ions separated in time according to mobility directly to an ion accelerating region of a time-of-flight mass analyzer. The ions are generated in the ion source and transferred to the mobility separator. The mobility separator is operated by injecting a pulse of ions into the drift region which is filled with a gas and comprises a substantially constant (uniform) electric field along its axis. The ion pulse is generated by a gating device which is located at the entrance of the drift region and capable of injecting ions into the drift region for only a short time span of typically less than a few hundred microseconds. The injected ions are dragged through the gas by the constant electric field. The friction with the gas results in a constant drift velocity vd for each ion species that is proportional to the electric field strength E: vd=μ·E. The proportionality factor μ is called the “ion mobility coefficient” of the ion species. The mobility μ is a function of gas temperature, gas pressure, type of gas, ion charge and, in particular, the ion neutral collision cross-section.
This kind of drift type mobility separator can be operated at pressures between approximately 10 Pa and more than atmospheric pressure. At low pressures between 10 Pa and 2000 Pa, the length of the drift region is typically one to four meters and the electric field strength is between one to three kilovolts per meter. The drift times of ions are typically about 1 to 100 milliseconds. In contrast to mobility separators which are operated at atmospheric pressure, the formation of complex ions by reactions with the drift gas, or impurities contained in the drift gas, is very low at low pressures and can be neglected. This fact makes low pressure ion mobility spectrometry capable to precisely determine ion-neutral collision cross sections. Furthermore, low pressure ion mobility spectrometers can be more easily coupled with mass analyzers operating under vacuum.
The mobility resolution is defined as R=μ/Δμ=vd/Δvd , where Δμ is the width of the ion signal at half height, and Δvd is the correspondent difference in velocity. The mobility resolution R of a mobility separator with a constant electric drift field is predominantly influenced by the electric field strength, the ion charge state, the temperature and the duration of the ion injection. Other effects, such as space charge and electric field inhomogeneity normally tend to be negligibly small.
FIG. 1 shows a drift type mobility separator with a drift tube (4) and Bradbury-Nielsen grid (2) as gating device. The Bradbury-Nielsen grid (2) comprises bipolar grids with positive/negative DC voltages. Ions (1) from an ion source (not shown) are guided toward the bipolar Bradbury-Nielsen grid (2) and stopped there by discharging at the Bradbury-Nielsen grid (2). If the bipolar DC voltages at the Bradbury-Nielsen grid (2) are switched off, part of the ions are transmitted through the Bradbury-Nielsen grid (2) and enter the drift tube (4). During the drift, the ion species (9a, 9b, 9c) are separated in time according to their different drift velocities. The drift tube electrodes (8) typically have a wide inner diameter and allow injected ions (9a, 9b, 9c) to expand radially by diffusion in the gas. The separated ion species (9a, 9b, 9c) are guided to a downstream mass analyzer (5). A disadvantage of using a Bradbury-Nielsen grid (2) as a gating device is that only a small fraction of the ion population (1) is transferred to the entrance of the drift tube (4), injected into the drift tube (4) and further analyzed.
Higher utilization of ions, and thus a better sensitivity, can be achieved by trapping ions in an ion storage device located in front of the drift tube and injecting ions from the ion storage device into the drift tube. The trapping of ions at the entrance of a drift-type mobility separator is disclosed in the U.S. Pat. No. 5,905,258.
U.S. Pat. No. 6,818,890 (Smith et al.) discloses a drift-type mobility separator with a specific ion storage device at the entrance of a drift tube. FIG. 2 shows a schematic of this drift-type mobility separator. The specific ion storage is an RF ion funnel (6). The ion population (7) transferred from ion source to the entrance of the drift tube (4) is trapped within the RF ion funnel (6), and pulsed out into the drift tube (4) within a short time span of typically less than a millisecond. Within the trapping region of the RF ion funnel (6), the electrodes (8) are operated by a superposition of RF and DC voltages. The RF voltages keep the ions away from the electrodes (8), and the DC voltages push the ions towards the opening of the funnel. The ions can be accumulated in the RF ion funnel (6) during the time in which previously injected ions drift through the drift tube (4). By regulating the DC and/or RF voltages, the RF ion funnel (6) can be closed or opened to release ions from RF ion funnel (6) into the drift region (4). During the drift, the ion species (9a, 9b, 9c) are separated in time according to their different drift velocities. The drift tube electrodes (8) typically have a wide inner diameter and allow the ions (9a, 9b, 9c) to expand radially by diffusion in the gas. A second RF ion funnel (not shown) can be located at the end of the drift tube (4) in order to refocus the radially expanded and separated ions (9a, 9b, 9c) on the axis of drift tube (4). The separated ion species (9a, 9b, 9c) are guided to a downstream mass analyzer (5).
U.S. Pat. No. 6,639,213 (Gillig et al.) discloses drift-type mobility separators that use periodic focusing electric DC fields in order minimize the spatial spread of migrating ions by keeping them in a tight radius about the axis of travel. The periodic focusing electric DC fields are substantially constant in time.
U.S. Pat. No. 6,791,078 (Giles et al.) discloses a different type of mobility separator. Unlike the drift-type mobility separators which utilize a constant electric field across the entire drift region, the travelling wave mobility separator consists of a stacked-ring RF ion guide that applies a repeating sequence of transient DC voltages with a specific wave height, speed, and velocity to the ring electrodes.
Ions from an ion source are transferred to an ion storage device at the entrance of the travelling wave mobility separator. Like the drift type mobility separator, the travelling wave mobility separator is operated by injecting a pulse of ions into a drift region. The transient DC voltages generate a traveling electric field that propels the injected ions through the gas filled drift region. The drift time it takes for an ion to drift through the drift region depends on its mobility as well as the wave height, speed, velocity, as well as the gas pressure. Ion species with high mobility are better able to keep up with traveling waves and are pushed more quickly through the drift region. Ion species with low mobility crest over the waves more often and have to wait for subsequent waves to push them forward, resulting in longer drift times. The different ion species, separated in time according to their mobility, are guided to a downstream mass analyzer which is typically a time-of-flight mass analyzer with orthogonal ion injection.
The resolution of a traveling wave mobility separator is affected by the travelling wave height, speed, and velocity, the gas pressure and also by the duration of ion injection.
There is still a need for methods and devices for effectively trapping and injecting ions into the drift region of a drift-type or traveling wave mobility separator, in particular, in case of high ion currents from the ion source and thus, high space charge in the trapping region. The number of injected ions should be higher than in devices according to the state of the art without sacrificing the mobility resolution of the mobility separator.